Unlike native proteins that are amenable to structural analysis at atomic resolution, unfolded proteins occupy a manifold of dynamically interconverting structures. Defining the conformations of unfolded proteins is of significant interest and importance, for folding studies and for understanding the properties of intrinsically disordered proteins. Short chain protein fragments, i.e., oligopept...

Title of dissertation: CONFORMATIONAL SAMPLING AND CALCULATION OF MOLECULAR FREE ENERGIES USING SUPERPOSITION APPROXIMATIONS Sandeep Somani, Doctor of Philosophy, 2011 Dissertation directed by: Professor Michael K Gilson University of Maryland College Park The superposition approximations (SAs), first proposed in the distribution function theories of liquids, are a family of approximations to a...

The conformational landscape of HIV-1 protease (PR) can be experimentally characterized by pulsed-EPR double electron-electron resonance (DEER). For this characterization, nitroxide spin labels are attached to an engineered cysteine residue in the flap region of HIV-1 PR. DEER distance measurements from spin-labels contained within each flap of the homodimer provide a detailed description of th...

Protein conformational transitions, which are essential for function, may be driven either by entropy or enthalpy when molecular systems comprising solute and solvent molecules are the focus[1, 2]. Revealing thermodynamic origin of a given molecular process is an important but difficult task, and general principles governing protein conformational distributions remain elusive. Here we demonstra...

The decryption of sequence of structural events during protein conformational transitions is essential to a detailed understanding of molecular functions of various biological nanomachines. Coarse-grained models have proven useful by allowing highly efficient simulations of protein conformational dynamics. By combining two coarse-grained elastic network models constructed based on the beginning...

A conformational epitope is composed of several discontinuous segments as antigenic determinants which are spatially close to each other in the three dimensional structure. These segments form the antigen which may bind with a specific receptor of the immune system, and play an important role in vaccine designs and immuno-biological experiments. Though there are two major types of epitopes: lin...

The probability distribution of isomeric conformations in poly(dimethylsi1oxane) has been investigated both by conformational energy considerations and by molecular dynamics simulations. A comparatively smooth distribution of isomeric states is obtained from both approaches. The molecular dynamics trajectory of a simulated dimethylsiloxane oligomer of eight units is used as a reliable and reali...

A novel numerical method for determining the conformational structure of macromolecules is applied to idealized biomacromolecules in solution. The method computes effective inter-residue interaction potentials solely from the corresponding radial distribution functions, such as would be obtained from experimental data. The interaction potentials generate conformational ensembles that reproduce ...

In this study, we theoretically investigated Methyl hydrazinecarbodithioate by quantum chemical calculations for geometry optimization, vibration frequencies, and electronic structure parameters. The geometry optimization by DFT, ab initio MP2 method and the frequency calculation by DFT method was performed at the highest available Pople style 6-311G++(3df,3pd) basis set level. The semi-emp...

A key step in drug development is the identification of both a protein target and its topological cellular network location and interactions, with regard to information flow in disease-causing events and to medication effects. Information flow involves a cascade of binding or covalent modification processes, with each step being affected by those that occur previously. Proteins are flexible, an...